1. Technical Field
The present invention generally relates to a stable topical pharmaceutical composition for the treatment of Acne vulgaris comprising adapalene or a pharmaceutically acceptable salt thereof and benzoyl peroxide and a process for preparing the same.
2. Description of the Related Art
Acne vulgaris is an inflammatory disease of the sebaceous glands characterized by an eruption of the skin, often pustular in nature but not supportive. Acne is a common affliction of the adolescent and affects a small but significant percentage of the adult population. Acne involvement results in unsightly lesions, particularly on the face, and in some cases results in severe scarring.
There are a variety of methods of administering various agents for treating Acne vulgaris, including either orally or topically to the skin. Nevertheless, Acne vulgaris is seldom cured and only can be controlled with difficulty. In no case has a treatment designed for any of the aforementioned causes proven to be uniformly effective. The market is replete with products that contain single component topical skin ointments, where such components may contain, inter alia, benzoyl peroxide or adapalene.
Of the more typical ingredients in topical treatments are benzoyl peroxide (BPO) and adapalene, which are known to be effective in treating mild to moderate cases of non-inflammatory acne. Benzoyl peroxide acts by destroying Pseudomonas acnes, the bacteria that causes the condition acne. Benzoyl peroxide acts as an antiseptic and as an oxidizing agent, reducing the number of comedones, or blocked pores. While, adapalene, otherwise known as 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid, is purported to bind to specific retinoic acid nuclear receptors but not to the cytosolic receptor protein. Although the exact mode of action of adapalene is unknown, it had been suggested that topical adapalene may normalize the differentiation of follicular epithelial cells resulting in decreased microcomedone formation. Ideally, a combination drug should have both comedogenesis and bacteriostatic effect in acne treatment. However, an obstacle to a combination utilizing adapalene is the instability of adapalene in the presence of BPO.
The market also offers dual component anti-acne compositions. Some of which are as described. Commercial composition EPIDUO® comprises adapalene 0.1%; and benzoyl peroxide 2.5% in the form of aqueous gel with inactive ingredients acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, POLOXAMER™124, polysorbate 80, propylene glycol, purified water, and sorbitan oleate.
U.S. Pat. No. 7,820,186 describes aqueous gel composition for once-daily treatment of common acne comprising anti-acne actives consisting of 0.1% adapalene and/or at least one pharmaceutically acceptable salt thereof, 2.5% dispersed benzoyl peroxide, and further comprising 4% acrylamide sodium acryloyldimethyltaurate copolymer/isohexadecane/polysorbate 80 gelling agent. The gelling agent described is a pH independent gelling agent.
WO PCT International Publication No. 2009092954 describes composition comprising, at least one retinoid and dispersed benzoyl peroxide and at least one gelling agent from carrageenan family.
U.S. Pre-grant Publication No. US2010/0166852 describes a cream gel dermatological composition useful for the prevention or treatment of dermatological conditions, comprising a homogeneous dispersion of a fatty phase in an aqueous phase, including at least one dispersed retinoid and dispersed benzoyl peroxide, at least one lipophilic compound and at least one gelling agent.
U.S. Pre-grant Publication No. 2009/0253788 directed to a treatment regimen for reducing the number of acne lesions, comprising administering a combination composition which comprises adapalene or a pharmaceutically acceptable salt thereof and benzoyl peroxide.
The pH independent gelling polymers described in the prior art are expensive. The present invention presents a cost-effective stable composition of adapalene and benzoyl peroxide with easily procured pH dependent gelling polymers; and the process of preparation can be upscaled for commercial usage.